Plasma Lipoprotein Phenotype in Response to Cholesteryl Ester Transfer Protein Levels in Dyslipoproteinemia
There are two mamallian systems for reverse cholesterol transport, one of which is dependent on the presence of cholesteryl ester transfer protein (CETP) activity1,2. The rat is typical of species lacking CETP activity and under these conditions, triglyceride-rich lipoproteins and their remnants transport only that cholesterol which was initially associated with the nascent particles. Rat HDL on the other hand, is rich in apoE and transports cholesterol derived from both splanchnic and peripheral organs, and esterified by LCAT and eventually returns it to the liver, via an apoE receptor. In contrast in the human system, the high CETP activity promotes the transfer of 2/3 or more of cholesteryl esters in HDL to the triglyceride-rich lipoproteins and their remnants. These recipient jparticles are then actively removed by hepatic apoE and apoB/E receptors3. In individuals with active receptors, this represents the major pathway for reverse cholesterol transport while a minority of HDL cholesterol is cleared directly by an apoE-mediated pathway. Direct selective uptake of HDL cholesteryl esters by the liver has also been suggested, but recent evidence indicated that this route is also apoE-mediated4.
KeywordsCholesteryl Ester Cholesteryl Ester Transfer Protein Reverse Cholesterol Transport Cholesteryl Ester Transfer Protein Activity Familial Combine Hyperlipidemia
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- 2.Y.C. Ha, and P.J. Barter, Differences in plasma cholesteryl ester transfer activity in sixteen vertebrate species, Comp. Biochem. Physiol. 71B:265 (1982).Google Scholar
- 4.F. Rinniger, and R.C. Pitman, Mechanism of cholesteryl ester transfer protein-mediated uptake of high density lipoprotein cholesteryl esters by HepG2 cells, J. Biol. Chem. 264:6118 (1989).Google Scholar
- J. Koizumi, H. Mabuchi, A. Yoshimura, I. Michishita, M. Takeda, H. Itoh, Y. Sakai, T. Sakai, K. Ueda, and R. Takeda, Deficiency of serum cholesteryl ester transfer activity in patients with familial hyperalphalipoproteinemia.Google Scholar
- Lipid Research Clinics Program, in Manual of Laboratory operations. U.S. Government printing office, Bethesda Md, p. 1–81 (1974).Google Scholar
- E.M. Quinet, L.B. Agellon, P.A., Kroon, Y.L. Marcel, Y.C. Lee, M.E. Whitlock, and A.R. Tall, Atherogenic diet increased cholesteryl ester transfer protein mRNA levels in rabbit liver, J. Clin. Invest. 85:357 (19??).Google Scholar
- R. McPherson, M. Hogue, R.U. Milne, A.R. Tall, and Y.L. Marcel, Increase in plasma cholesteryl ester transfer protein during Probucol treatment: relationship to changes in HDL compostion, submitted for publication.Google Scholar